3uvw

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of the first bromodomain of human BRD4 in complex with a diacetylated histone 4 peptide (H4K5acK8ac)

Structural highlights

3uvw is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.37Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

BRD4_HUMAN Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.^[1] ^[2]

Function

BRD4_HUMAN Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).

Publication Abstract from PubMed

Bromodomains (BRDs) are protein interaction modules that specifically recognize epsilon-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family.

Histone recognition and large-scale structural analysis of the human bromodomain family.,Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S Cell. 2012 Mar 30;149(1):214-31. PMID:22464331^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003 Jan 15;63(2):304-7. PMID:12543779
↑ French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, Vargas SO, Perez-Atayde AR, Fletcher JA. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol. 2001 Dec;159(6):1987-92. PMID:11733348 doi:10.1016/S0002-9440(10)63049-0
↑ Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S. Histone recognition and large-scale structural analysis of the human bromodomain family. Cell. 2012 Mar 30;149(1):214-31. PMID:22464331 doi:10.1016/j.cell.2012.02.013

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3uvw"

@@ Line 1: / Line 1: @@
-{{STRUCTURE_3uvw|  PDB=3uvw  |  SCENE=  }}
-===Crystal Structure of the first bromodomain of human BRD4 in complex with a diacetylated histone 4 peptide (H4K5acK8ac)===
-{{ABSTRACT_PUBMED_22464331}}
-==Disease==
+==Crystal Structure of the first bromodomain of human BRD4 in complex with a diacetylated histone 4 peptide (H4K5acK8ac)==
-[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref><ref>PMID:11733348</ref>
+<StructureSection load='3uvw' size='340' side='right'caption='[[3uvw]], [[Resolution|resolution]] 1.37&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3uvw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UVW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UVW FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.37&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3uvw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uvw OCA], [https://pdbe.org/3uvw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uvw RCSB], [https://www.ebi.ac.uk/pdbsum/3uvw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uvw ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Bromodomains (BRDs) are protein interaction modules that specifically recognize epsilon-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family.
-==Function==
+Histone recognition and large-scale structural analysis of the human bromodomain family.,Filippakopoulos P, Picaud S, Mangos M, Keates T, Lambert JP, Barsyte-Lovejoy D, Felletar I, Volkmer R, Muller S, Pawson T, Gingras AC, Arrowsmith CH, Knapp S Cell. 2012 Mar 30;149(1):214-31. PMID:22464331<ref>PMID:22464331</ref>
-[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[3uvw]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UVW OCA].
+</div>
+<div class="pdbe-citations 3uvw" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-<ref group="xtra">PMID:022464331</ref><references group="xtra"/><references/>
+*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Arrowsmith, C H.]]
+[[Category: Large Structures]]
-[[Category: Bountra, C.]]
+[[Category: Arrowsmith CH]]
-[[Category: Delft, F von.]]
+[[Category: Bountra C]]
-[[Category: Edwards, A M.]]
+[[Category: Edwards AM]]
-[[Category: Felletar, I.]]
+[[Category: Felletar I]]
-[[Category: Filippakopoulos, P.]]
+[[Category: Filippakopoulos P]]
-[[Category: Gileadi, O.]]
+[[Category: Gileadi O]]
-[[Category: Keates, T.]]
+[[Category: Keates T]]
-[[Category: Knapp, S.]]
+[[Category: Knapp S]]
-[[Category: Muniz, J.]]
+[[Category: Muniz J]]
-[[Category: Picaud, S.]]
+[[Category: Picaud S]]
-[[Category: SGC, Structural Genomics Consortium.]]
+[[Category: Weigelt J]]
-[[Category: Weigelt, J.]]
+[[Category: Von Delft F]]
-[[Category: Bromodomain]]
-[[Category: Bromodomain containing protein 4]]
-[[Category: Cap]]
-[[Category: Hunk1]]
-[[Category: Mcap]]
-[[Category: Mitotic chromosome associated protein]]
-[[Category: Peptide complex]]
-[[Category: Protein binding]]
-[[Category: Sgc]]
-[[Category: Structural genomics consortium]]
-[[Category: Transcription]]
-[[Category: Transcription-protein binding complex]]

3uvw

From Proteopedia

Current revision

Crystal Structure of the first bromodomain of human BRD4 in complex with a diacetylated histone 4 peptide (H4K5acK8ac)

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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